For which infants with viral bronchiolitis could it be deemed appropriate to use albuterol, at least on a therapeutic trial basis?

Main Article Content

Carlos E. Rodríguez-Martínez
Gustavo Nino
Jose A. Castro-Rodriguez
Ranniery Acuña-Cordero
Monica P. Sossa-Briceño
Fabio Midulla


bronchiolitis, viral bronchiolitis phenotyping, clinical practice guidelines, phenotype-specific treatment.


Although there is increasing evidence showing that infants with viral bronchiolitis exhibit a high degree of heterogeneity, a core uncertainty shared by many clinicians is with regard to understanding which patients are most likely to benefit from bronchodilators such as albuterol. Based on our review, we concluded that older infants with rhinovirus (RV) bronchiolitis, especially those with a nasopharyngeal microbiome dominated by Haemophilus influenzae; those affected during nonpeak months or during non-respiratory syncytial virus (RSV) predominant months; those with wheezing at presentation; those with clinical characteristics such as atopic dermatitis or a family history of asthma in a first-degree relative; and those infants infected with RSV genotypes ON1 and BA, have the greatest likelihood of benefiting from albuterol. Presently, this patient profile could serve as the basis for rational albuterol administration in patients with viral bronchiolitis, at least on a therapeutic trial basis, and it could also be the starting point for future targeted randomized clinical trials (RCTs) on the use of albuterol among a subset of infants with bronchiolitis.

Abstract 1605 | PDF Downloads 1461 HTML Downloads 748 XML Downloads 93


1. Leader S, Kohlhase K. Recent trends in severe respiratory syncytial virus (RSV) among US infants, 1997 to 2000. J Pediatr. 2003;143(5 Suppl):S127–S132. 10.1067/s0022-3476(03)00510-9

2. Scheltema NM, Gentile A, Lucion F, Nokes DJ, Munywoki PK, Madhi SA, et al. Global respiratory syncytial virus associated mortality in young children (RSV GOLD): A retrospective case series. Lancet Global Health. 2017;5(10):e984–e991. 10.1016/S2214-109X(17)30349-2

3. Paramore LC, Ciuryla V, Ciesla G, Liu L. Economic impact of respiratory syncytial virus-related illness in the US: An analysis of national databases. PharmacoEconomics. 2004;22(5):275–284. 10.2165/00019053-200422050-00001

4. Diagnosis and management of bronchiolitis. Pediatrics. 2006;118(4):1774–1793. 10.1542/peds.2006-2223

5. Ralston SL, Lieberthal AS, Meissner HC, Alverson BK, Baley JE, Gadomski AM, et al. Clinical practice guideline: The diagnosis, management, and prevention of bronchiolitis. Pediatrics. 2014;134(5):e1474–e1502. 10.1542/peds.2014-2742

6. Ricci V, Delgado Nunes V, Murphy MS, Cunningham S. Bronchiolitis in children: Summary of NICE guidance. BMJ (Clinical research ed). 2015;350:h2305. 10.1136/bmj.h2305

7. Rodriguez-Martinez CE, Castro-Rodriguez JA, Nino G, Midulla F. The impact of viral bronchiolitis phenotyping: Is it time to consider phenotype-specific responses to individualize pharmacological management? Paediatr Respir Rev. 2020;34:53–58. 10.1016/j.prrv.2019.04.003

8. Rodriguez-Martinez CE, Castro-Rodriguez JA. Bronchodilators should be considered for all patients with acute bronchiolitis, but closely monitored for objectively measured clinical benefits. Acta Paediatrica (Oslo, Norway: 1992). 2015;104(9):858–860. 10.1111/apa.13051

9. Rodriguez-Martinez CE, Castro-Rodriguez JA. Children under 12 months could benefit from a therapeutic trial with bronchodilators if the clinical response is positive. Acta Paediatrica (Oslo, Norway: 1992). 2015;104(12):e540. 10.1111/apa.13218

10. Seumois G, Zapardiel-Gonzalo J, White B, Singh D, Schulten V, Dillon M, et al. Transcriptional profiling of Th2 cells identifies pathogenic features associated with asthma. J Immunol (Baltimore, MD: 1950). 2016;197(2):655–664. 10.4049/jimmunol.1600397

11. Midulla F, Scagnolari C, Bonci E, Pierangeli A, Antonelli G, De Angelis D, et al. Respiratory syncytial virus, human bocavirus and rhinovirus bronchiolitis in infants. Arch Dis Child. 2010;95(1):35–41. 10.1136/adc.2008.153361

12. Fedele G, Schiavoni I, Nenna R, Pierangeli A, Frassanito A, Leone P, et al. Analysis of the immune response in infants hospitalized with viral bronchiolitis shows different Th1/Th2 profiles associated with respiratory syncytial virus and human rhinovirus. Pediatr Allergy Immunol. 2018;29(5):555–557. 10.1111/pai.12919

13. Pierangeli A, Statzu M, Nenna R, Santinelli L, Petrarca L, Frassanito A, et al. Interferon lambda receptor 1 (IFNL1R) transcript is highly expressed in rhinovirus bronchiolitis and correlates with disease severity.J Clin Virol. 2018;102:101–109. 10.1016/j.jcv.2018.03.003

14. Hasegawa K, Perez-Losada M, Hoptay CE, Epstein S, Mansbach JM, Teach SJ, et al. RSV vs. rhinovirus bronchiolitis: Difference in nasal airway microRNA profiles and NFkappa B signaling. Pediatr Res. 2018;83(3):606–614. 10.1038/pr.2017.309

15. Stewart CJ, Hasegawa K, Wong MC, Ajami NJ, Petrosino JF, Piedra PA, et al. Respiratory syncytial virus and rhinovirus bronchiolitis are associated with distinct metabolic pathways. J Infect Dis. 2018;217(7):1160–1169. 10.1093/infdis/jix680

16. Zhang X, Zhang X, Zhang N, Wang X, Sun L, Chen N, et al. Airway microbiome, host immune response and recurrent wheezing in infants with severe respiratory syncytial virus bronchiolitis. Pediatr Allergy Immunol. 2019;31(3):281–289. 10.1111/pai.13183

17. Mansbach JM, Clark S, Teach SJ, Gern JE, Piedra PA, Sullivan AF, et al. Children hospitalized with rhinovirus bronchiolitis have asthma-like characteristics. J Pediatr. 2016;172:202.e201–204.e201. 10.1016/j.jpeds.2016.01.041

18. Mansbach JM, Piedra PA, Teach SJ, Sullivan AF, Forgey T, Clark S, et al. Prospective multicenter study of viral etiology and hospital length of stay in children with severe bronchiolitis. Arch Pediatr Adolesc Med. 2012;166(8):700–706. 10.1001/archpediatrics.2011.1669

19. Jackson DJ, Gangnon RE, Evans MD, Roberg KA, Anderson EL, Pappas TE, et al. Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am J Respir Crit Care Med. 2008;178(7):667–672. 10.1164/rccm.200802-309OC

20. Rubner FJ, Jackson DJ, Evans MD, Gangnon RE, Tisler CJ, Pappas TE, et al. Early life rhinovirus wheezing, allergic sensitization, and asthma risk at adolescence. J Allergy Clin Immunol. 2017;139(2):501–507. 10.1016/j.jaci.2016.03.049

21. Carroll KN, Wu P, Gebretsadik T, Griffin MR, Dupont WD, Mitchel EF, et al. Season of infant bronchiolitis and estimates of subsequent risk and burden of early childhood asthma. J Allergy Clin Immunol. 2009;123(4):964–966. 10.1016/j.jaci.2008.12.011

22. Martinez FD. Childhood asthma inception and progression: Role of microbial exposures, susceptibility to viruses and early allergic sensitization. Immunol Allergy Clin. 2019;39(2):141–150. 10.1016/j.iac.2018.12.001

23. Cangiano G, Nenna R, Frassanito A, Evangelisti M, Nicolai A, Scagnolari C, et al. Bronchiolitis: Analysis of 10 consecutive epidemic seasons. Pediatr Pulmonol. 2016;51(12):1330–1335. 10.1002/ppul.23476

24. Nenna R, Frassanito A, Petrarca L, Di Mattia G, Pierangeli A, Scagnolari C, et al. RSV bronchiolitis in infants hospitalized during the epidemic peak and non-peak months: Different Th1/Th2 response. Am J Respir Crit Care Med. 2018;197:A2865.

25. Dumas O, Mansbach JM, Jartti T, Hasegawa K, Sullivan AF, Piedra PA, et al. A clustering approach to identify severe bronchiolitis profiles in children. Thorax. 2016;71(8):712–718. 10.1136/thoraxjnl-2016-208535

26. Flores G, Horwitz RI. Efficacy of beta2-agonists in bronchiolitis: A reappraisal and meta-analysis. Pediatrics. 1997;100(2 Pt 1):233–239. 10.1542/peds.100.2.233

27. Kellner JD, Ohlsson A, Gadomski AM, Wang EE. Efficacy of bronchodilator therapy in bronchiolitis. A meta-analysis. Arch Pediatr Adolesc Med. 1996;150(11):1166–1172. 10.1001/archpedi.1996.02170360056009

28. Pina-Hincapié SM., Sossa-Briceno MP., Rodriguez-Martinez CE. Predictors for the prescription of albuterol in infants hospitalized for viral bronchiolitis. Alergol Immunopathol. 2020 (in press).

29. Condella A, Mansbach JM, Hasegawa K, Dayan PS, Sullivan AF, Espinola JA, et al. Multicenter study of albuterol use among infants hospitalized with bronchiolitis. West J Emerg Med. 2018;19(3):475–483. 10.5811/westjem.2018.3.35837

30. Arroyo M, Salka KP, Perez GF, Rodriguez-Martinez CE, Castro-Rodriguez JA, Nino G. Bedside clinical assessment predicts recurrence after hospitalization due to viral lower respiratory tract infection in young children. J Investig Med. 2019;68(3):756–761. 10.1136/jim-2019-001024

31. Arroyo Morr KSMA, Perez G, Jackson JH, Pillai DK, Rodriguez-Martinez CE, Nino GR. Redefining bronchiolitis: Respiratory phenotyping of viral lower respiratory tract infections identifies subsets with distinct acute severity and recurrence of respiratory illnesses during early life. Am J Respir Crit Care Med. 2018;197:A2861.

32. Carande EJ, Pollard AJ, Drysdale SB. Management of respiratory syncytial virus bronchiolitis: 2015 Survey of members of the European Society for Paediatric Infectious Diseases. Can J Infect Dis Med Microbiol. 2016;2016:9139537. 10.1155/2016/9139537

33. Elenius V, Bergroth E, Koponen P, Remes S, Piedra PA, Espinola JA, et al. Marked variability observed in inpatient management of bronchiolitis in three Finnish hospitals. Acta Paediatrica (Oslo, Norway: 1992). 2017;106(9):1512–1518. 10.1111/apa.13931

34. Sarmiento L, Rojas-Soto GE, Rodriguez-Martinez CE. Predictors of inappropriate use of diagnostic tests and management of bronchiolitis. BioMed Res Int. 2017;2017:9730696. 10.1155/2017/9730696

35. Alansari K, Sakran M, Davidson BL, Ibrahim K, Alrefai M, Zakaria I. Oral dexamethasone for bronchiolitis: A randomized trial. Pediatrics. 2013;132(4):e810–e816. 10.1542/peds.2012-3746

36. Marchand D, Tayara N, Choukroun ML, Sarrat A, Guenard H, Demarquez JL, et al. [Atopic dermatitis aggravates the allergic airways inflammation in acute viral bronchiolitis]. Revue des maladies respiratoires. 2008;25(9):1087–1093. 10.1016/S0761-8425(08)74978-7

37. Midulla F, Nenna R, Scagnolari C, Petrarca L, Frassanito A, Viscido A, et al. How respiratory syncytial virus genotypes influence the clinical course in infants hospitalized for bronchiolitis. J Infect Dis. 2019;219(4):526–534. 10.1093/infdis/jiy496